peroxynitrite more involved than realized ?

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
Interesting and timely thread on these conflicting hypotheses.

Back in 2004 I went from 40% to about 80% within about 2-3 weeks after my doc at the time prescribed methyl-b12 shots along with nebulized glutathione. I did the glutathione for about six weeks and the b12 for about six months, then thiamine injections for 2 months. The improvement lasted about a year, then I ran out of funds, stress increased 10,000% (well, maybe 9,999%), and crashed back to 40-50% or so. And thanks to time and brain fog, I totally forgot about the methyl-b12 injections until late 2011-early 2012.

Since then I've been doing methylation off and on for several years and continue to deteriorate. Now this could be due to many factors. I had a bad reaction at first (late 2010), panicked, and restarted cautiously 8 months later. As a result I haven't stuck with a specific amount of the various nutrients on a consistent basis, so that may explain part of my poor results. Also haven't been able to afford any injections, except for one round of thiamine (which helped) this past January.

I definitely notice periods however where I suddenly feel a little better, more optimistic, more 'energy' an hour or so after a b12 sublingual. But it's not consistent. Same with folinic acid. It definitely helps me sleep -- very deeply sometimes -- but the amount I need to take seems to vary quite a bit. Again, maybe this would change if I took it 3-4 times a day regularly?

Anyway, because of these mixed reactions, and overall downward trend, I'll dump anything that might be causing problems and am open to trying a different approach.

Martin Pall came and spoke to our local group back in 2006-2007, and came off as very genuine and sincerely committed to his hypothesis. Makes sense as he developed it to recover from his MCS.

But there are others out there who suggest that we're taking too many antioxidants as it is, and that in doing so, we're interfering with normal immune function.

One who disagrees with Pall is Randolph M. Howes M.D, this from an email from 2007 (already!):

"First, I do not accept the so-called concept of oxidative stress that was proposed by Sies. Oxidation is the primary process which protects us from pathogens, such as bacteria, viruses, protozoans, fungi and cancer. Thus, I believe that it is unsafe to promote the ingestion large quantities of antioxidants."

When he expressed doubt that CFS is a real disease, I replied assuring him that it was, and here is part of his reply:

"t is not very well known but the father of the free radical theory, Dr. Denham Harman, stated in a conversation with Jack Cheatum that ingestion of too much of the antioxidants will lead to "fatigue." This makes sense, since the antioxidants are trying to interfere with the electron transport chain, which is the major energy generating system in the body and produces ATP.

Actually, I have speculated in some of my writings that overuse of antioxidants may be in part responsible for the increase in chronic fatigue syndrome but this too is purely speculative. You mentioned a weakened immune system and please keep in mind that the immune system protects us by using oxidative agents, such as hyrogen peroxide, superoxide anion, singlet oxygen, hypchlorous acid and possibly ozone. Prooxidants are crucial to a healthy immune system."

And then there's Dave Whitlock, who completely disagrees with Dr. Pall. I've been intrigued by Whitlock's hypothesis as well, but also don't quite understand it. But while googling on another issue I came across this by Whitlock, which is interesting -- suggesting that we've gone overboard with our modern hygiene practices, leading to a loss of nitrate producing bacteria and increased rates of chronic illness:

https://books.google.com/books?id=a3mwmXzpsjkC&lpg=PP1&pg=PA103&hl=en#v=onepage&q&f=false

@JPV -- I wasn't aware that Whitlock had a product out, and couldn't find it for sale on a quick search. Do you have more info or have you been able to purchase it?
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Likes
1,080
I wasn't aware that Whitlock had a product out, and couldn't find it for sale on a quick search. Do you have more info or have you been able to purchase it?
Yes, you can get it here. It's a bit expensive, about $100.00USD for a 1 month supply, but there's a 25% discount code available here on Paul Jaminet's site. Delivery takes about a week.

I've been using it for about a week now. I've had a couple of good days but it's too soon and random to be able attribute these to using the AO+ Mist. I feel like it might be a bit inconsistent. I think the bacteria contained in it is entirely dependent on sweat for food. Since I don't sweat much these days, and suffer too much from PEM to be able to exercise a lot, I'm not sure that I'm giving it enough substrate to work very efficiently. I try to go for walks in the sun but it's hard to know if this is enough to activate it properly.

Keep in mind that it's currently being marketed as a beauty product, pending FDA approval for health claims, so I wonder if the dosage is even of a therapeutic level. Maybe he intends on doing different version of the product after FDA approval, I don't know. Whitlock has spoken a lot about NO in relationship to Autism and ME/CFS in the past but since the product has been introduced, he seems to be more hesitant to talk about this aspect of the product. I don't take this as him waffling so much as exhibiting caution during the FDA approval process.

I don't want to dissuade anyone from experimenting with a potentially beneficial intervention, but I'm not totally comfortable recommending this product to anyone else quite yet. I think I need to give it a longer trial. I also have a bad habit of trying too many things at one time, so I'm not always the best judge of these things. Then again, we all respond so differently that I guess it behooves others to try it at some point, if they think it will be of benefit, just to get a better consensus.

I'm also experimenting with Beet Root Powder as an alternate and (theoretically) more consistent method of boosting NO. Again, to early to give any reliable feedback on this approach either.
 
Last edited:

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
There's a research paper due out in Dec 2015 that you can view on Researchgate. The cause of fatigue is inflammation leading to oxidative stress. Not just CFS but also Lyme, depression, neurological diseases, etc. Peroxynitrite at the heart of it all. Big review paper, well worth a read.
 

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
There's a research paper due out in Dec 2015 that you can view on Researchgate. The cause of fatigue is inflammation leading to oxidative stress. Not just CFS but also Lyme, depression, neurological diseases, etc. Peroxynitrite at the heart of it all. Big review paper, well worth a read.
But what's causing the inflammation? That's the $64,000,000 question I know, but that's why we're wondering if this issue should be dealt with by using methylation vitamins and antioxidants -- or cut back on the both -- especially the antioxidants, in order to allow the immune system to oxidize the bad guys.

I still don't understand the nitrate/nitrite >> peroxynitrite connection. :)

Do you have a link to the paper @Mimi?
 

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
Yes, you can get it here. It's a bit expensive, about $100.00USD for a 1 month supply, but there's a 25% discount code available here on Paul Jaminet's site. Delivery takes about a week.

I've been using it for about a week now. I've had a couple of good days but it's too soon and random to be able attribute these to using the AO+ Mist. I feel like it might be a bit inconsistent. I think the bacteria contained in it is entirely dependent on sweat for food. Since I don't sweat much these days, and suffer too much from PEM to be able to exercise a lot, I'm not sure that I'm giving it enough substrate to work very efficiently. I try to go for walks in the sun but it's hard to know if this is enough to activate it properly.

Keep in mind that it's currently being marketed as a beauty product, pending FDA approval for health claims, so I wonder if the dosage is even of a therapeutic level. Maybe he intends on doing different version of the product after FDA approval, I don't know. Whitlock has spoken a lot about NO in relationship to Autism and ME/CFS in the past but since the product has been introduced, he seems to be more hesitant to talk about this aspect of the product. I don't take this as him waffling so much as exhibiting caution during the FDA approval process.

I don't want to dissuade anyone from experimenting with a potentially beneficial intervention, but I'm not totally comfortable recommending this product to anyone else quite yet. I think I need to give it a longer trial. I also have a bad habit of trying too many things at one time, so I'm not always the best judge of these things. Then again, we all respond so differently that I guess it behooves others to try it at some point, if they think it will be of benefit, just to get a better consensus.

I'm also experimenting with Beet Root Powder as an alternate and (theoretically) more consistent method of boosting NO. Again, to early to give any reliable feedback on this approach either.
Thanks for the links @JPV -- very interesting. Too pricey for me right now, but still cool to see it finally come out.

I don't know if you checked out some of the comments on Jaminet's page, but someone mentioned that NO is produced in the nose too, so I wonder if it could be used there as well? Not suggesting you try it, but maybe a question to ask the elusive Mr. Whitlock. Makes sense though that he's being quiet though right now...

But also, someone in the comment section posted a link to this study, showing that humming increased nasal nitric oxide levels by 1500 percent:

http://www.atsjournals.org/doi/full/10.1164/rccm.200202-138BC#.VXIUpktV9EL

The soil bacteria-nitrate connection is also intriguing. Makes me wonder if "Prescript-Assist" might be worth a try.
 

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
Ommmmm! Thanks for that! I wonder if it applies to using other mantras? And since they make you feel blissful, if that means that they raise BH4??

Here is the paper on inflammation in ME/CFS
And here is the forthcoming paper on how inflammation causes fatigue in chronic illnesses generally due to increasing peroxynitrite which kills mitochondria and decreases BH4

As to causes of inflammation, I believe we all have an abundance of pathogens hiding underneath mega amounts of biofilm. Biofilms from fungi (molds and yeasts) are I think the most difficult to eradicate. There's a paper on bacterial-fungal interactions that says fungi protect bacteria and bacteria feed the fungi. That suggests to me that the fungi biofilms are a lot tougher. And probably bigger. But I think they all combine. Virus biofilms have also been discovered. So they probably all make big tent cities in our sinuses and in our guts. And from there, infection can go into the lymphatic system, which drains from the brain to the sinuses and out of the gut back into the brain. So plenty of opportunity for inflammation when you have a gazillion pathogens multiplying freely under the protective shelter of multi-layered biofilms. We've got major tent cities in there, folks! And we can't eradicate the pathogens until we dissolve the biofilms that protect them. Hence the chronic inflammation, fatigue and depression. That, and your usual culprits like toxic metals.

I've been corresponding with Dr. Brewer in Kansas City who is successfully treating ME/CFS patients with a combination of Nystatin nasal spray and far infrared (FIR) saunas. He currently has 400 patients under treatment and plans to publish a paper soon. So far he's had 30 patients recover, and I think it's because the biofilms melt at temperatures over 37 degrees Celsius. (Paper on that, too.) But also, it could be because heat shock proteins kill the mold directly, and that dismantles biofilms so that your immune system, or whatever drugs you are taking, can get at the microbes. The key seems to be mold, both avoiding it and clearing it. That unlocks the door to everything else.

Mimi
 
Last edited:

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
Thanks @Mimi. I'm familiar with Brewer's work -- wanted to do it a year ago -- and actually got tested, but the naturopath I was seeing wasn't familiar w/the protocol, and I got worse on her alternatives -- and then ran out of funds for a follow up. (I had forgotten though about the biofilm connection so thanks for the reminder, and the interesting bits on sauna or heat helping to break up the biofilm -- I wasn't aware of that. )

Back then Brewer was primarily using Ampho-B, and a lot of people had pretty bad reactions to that as well, so he moved on to trying Nystatin. Good to hear that some are recovering -- that's great, very encouraging. I wish I could afford to do it, but it's unlikely my medicaid doc (or medicaid itself) would approve/pay for it.

If anyone finds a winning lotto ticket, let me know. :)

And thanks @nandixon for the full papers.
 

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
Hi dannybex. I know how difficult it is on medicaid since I'm on medicaid myself. But I am saving my pennies for a portable far infrared sauna. Dr. Brewer told me one of his patients bought one on Amazon and "loves it". I found a low emf one that I've put on my wishlist - maybe find someone else who wants to use it and go in on it together? Or charge people a few dollars to come get sessions? I heard it's $30-$40 for sessions, so @$179 it will pay for itself.

Here is the one I wishlisted. There's another one for $175 but this one is low EMF. I haven't figured out the Nystatin prescription yet (still making my case to my PA, getting referrals from her) but I am on Lufenuron from Shop4Lufe. The owner is a very kind doctor from Mexico who runs an HIV/AIDS and cancer charity clinic. His English is nearly perfect and we've become close correspondents. Also, you might check out Kirkman Biofilm Defense.

Mimi
 
Last edited:

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
Thanks Mimi for the lnks and more info on the saunas -- much appreciated.

I have a question or two that will probably sound really stupid, but I got "C"s in math and science, so just to clarify: Peroxynitrite comes from nitrite and nitrate -- or what exactly is the connection if there is one?

I ask because nitrite and nitrates are very plentiful in green leafy vegetables, so it seems that if high levels of nitrate/nitrite aren't good (according to Pall and the other studies above) then wouldn't eating these wholesome (and folate rich) foods be a problem?
 

Kathevans

Senior Member
Messages
684
Likes
595
Location
Boston, Massachusetts
@dannybex and @Gondwanaland A doctor I saw in NYC for a couple of years prescribed Nadi Shodhana, or alternate nostril breathing as a way of balancing right and left hemispheres of the brain as well as increasing nitric oxide levels. Apparently the increase occurs on the In breath, as you draw air over your soft palate. The practice also regulates heart rate. I used it to bring my racing heart back into sinus rhythm. There are many scientific papers about its effects...

I found it very calming...
 

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
@Kathevans, wouldn't you know? There's a lot of wisdom in those ancient yogic practices.

dannybex, peroxynitrite is a combination of superoxide and nitric oxide. Normally, BH4 combines with arginine to make nitric oxide in what I heard is in a ratio of 2 BH4 molecules to 1 arginine. Nitric oxide causes the endothelial lining of your blood vessels to relax. It's critical for cardiovascular health. So NO is a good thing. We just didn't know that before.

When there isn't enough BH4 to make NO, superoxide forms instead. Superoxide rapidly combines with NO to make ONOO- or peroxynitrite. Peroxynitrite is a very dangerous oxidant that destroys mitochondria cell wells and generates free radicals - the hydroxyl radical in particular. But it's the peroxynitrite itself that appears to be the bigger problem.

As you can see from the papers I posted which nandixon was kind enough to link to in full, peroxynitrite causes inflammation. It also destroys BH4. As you have probably figured out, this is a problem, because the less BH4 you have the more you create peroxynitrite. This creates a vicious cycle which appears to be the root of chronic illness and fatigue.

So go ahead, eat those leafy greens. They're good for you. Nitric oxide is a good thing, and it's vital for your health. Dark greens in particular have a tremendous vitality and folate is required to recycle BH4. Having enough BH4 prevents the formation of peroxynitrite. If greens were bad for us then all the grazing animals on the planet would be dead.
 
Last edited:

dannybex

Senior Member
Messages
3,502
Likes
2,599
Location
Seattle
Okay, thanks, that's very helpful. Dr. Pall should hire you to write his protocol "For Dummies".

Just one more question however: I thought SOD stood for Superoxide Dismutase, which is a good compound isn't it?

In fact, I've had a bottle of Bitter Melon SOD that's been in the drawer for probably 9-10 months, and just started to take it about 10 days ago, and thought it was really making a difference. But the last 4-5 days I've experienced increase hip, lower back pain, so not sure if I should continue with it?
 

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
You're right. I'm going to edit the above. (Done!) Superoxide is not SOD. SOD, or superoxide dismutase, is what reduces superoxide so that it is destroyed. Bitter melon has a tremendous reputation in traditional Chinese medicine and my 72 year old acupuncture teacher swore by it. I think you just convinced me to start eating bitter melon on a regular basis :)

As for your hip and back pain, why don't you stop for a while and see if the pain goes away?
 
Last edited:

Mimi

Senior Member
Messages
203
Likes
136
Location
Medford, OR
@Kathevans, what do you want to bet that purring raises NO (and BH4!) in cats? It certainly seems to make them feel good. I wonder if that's because the kitties are raising their dopamine and serotonin?

Here' something I found on Curezone on how cats use the vibration of purring to heal themselves. A little off topic, but it might not be if the purring frequency raises BH4.
 
Last edited:

Gondwanaland

Senior Member
Messages
5,049
Likes
4,247
@Kathevans, what do you want to bet that purring raises NO (and BH4!) in cats? It certainly seems to make them feel good. I wonder if that's because the kitties are raising their dopamine and serotonin?
Hmmm so that is why they will also purr when they are in pain/ill.